Positive antibody & biopsy, negative genetics

[ShelbyE720]

I’m hoping someone here can give me some hope about my current situation!

I’ve spent the last 6 months seeing numerous doctors looking for answers to various wild problems I’m having. I went from perfectly healthy to quickly deteriorating over the course of the last few months. It started with extreme fatigue and cracking lips and turned into skin rashes (doesn’t look like DH though) chronically swollen lips, hair loss, anxiety, dizzy, extreme nausea, vomiting,chronic diarrhea. I lost 10lbs in 6 weeks. 
 

finally made it to GI specialist. Had a barely positive antibody test (15) for 1 antibody, but also had a positive biopsy (Villous atrophy with increased lymphocytes). I was told it was Celiac Disease and go gluten-free, so I did and my most extreme symptoms (vomiting/diarrhea) did stop. Meanwhile I had asked for the genetic testing to be really sure and to my surprise, I was negative for the genes associated with Celiac. My doctor then said “there’s no way it is Celiac Disease, maybe you improved bc you are just Gluten sensitive and just stay gluten-free if it helps”

So now I don’t know what to think! (I have also had a blood test to check for wheat allergy that was negative). Do I just stick to this diet hoping it’s an intolerance causing all these issues? Has anyone ever had Celiac without the common genes? Do I keep looking for other answers or accept it’s just NCGS? 

[trents]

Welcome to the forum, Shelby!

First, can you be more specific about which antibody test or tests were run and which one was positive? There are a number of antibody tests that can be used to detect celiac disease. Some are considered more specific for celiac disease while not being particularly sensitive. Some are less specific but more sensitive. Can you look up the tests that were run and which one was positive and post back with the info? Please include the reference ranges for negative vs. positive as each lab uses custom test concoctions such that there is no industry standard for the reference ranges.

Second, the endoscopy with biopsy is considered the gold standard for diagnosing celiac disease. There are only a very few things besides celiac disease that can cause villous atrophy in the small bowel. Rarely, intolerance to the dairy protein casein can cause villous atrophy, a certain blood pressure med and a tropical parasite and that's about it. NCGS (Non Celiac Gluten Sensitivity) does not cause villous atrophy and that factoid separates the two diagnostically speaking.

Third, research into the genetics of celiac disease is ongoing and it appears that there may be more than the two genes (DQ2 and DQ8) originally identified that are involved. IMO, your post here today corroborates that. Unfortunately, this information is not yet widely disseminated in the medical community yet and many practitioners are still leaning on the older model of two genes only. And by the way, I'm so glad you posted because it's strong evidence that there is more to the genetic picture than was formerly believed.

[ShelbyE720]

Trent’s,

thank you so much for replying! I’m pretty disheartened by my doctors lack of interest in my results. 

I had antibody testing at Quest for Transglutamimase AB IGG/IGA and Gliadin IGG/IGA. Of these tests, all results came back at a value of <1 EXCEPT the Transgltutiminase IGG came back at 15.46 (values for these were considered positive at a value of 15 or greater). These tests did not include my total IGA so I do not know if I am deficient. 

I did have both an endoscopy and colonoscopy done, as they were actually suspecting crohns. The colonoscopy only found some erythema and prominent lymphoids and a rather large pre-cancerous polyp that was removed. I am only 32 so this wasn’t expected and grateful it was removed. Bc of this, I will now have regular colonoscopy’s every 3 years, however signs of Crohns were not seen. 

I keep hearing that the endoscopy biopsy is the gold standard for celiac disease diagnosis, (results of mine clearly state in the report that “findings are highly indicative of celiac disease”), but with my doctor stating it can not be I just don’t know how serious to take a gluten-free diet. It makes me feel better (at least not vomiting, having diarrhea and able to eat again!) so I am sticking to it. I just have not been super careful about cross contamination since Celiac was “ruled out” by genetics.

[trents]

Let me challenge you on what seems to be your assumption that if you have NCGS instead of celiac disease that you don't have to be careful about cross contamination. We see this all the time on the forum. NCGS itself can lead to some serious damage to body systems. An example would be non celiac gluten induced neuropathy. We don't know as much about the immune system mechanism of NCGS as we do celiac disease. Some experts feel that NCGS can be a precursor to celiac disease. At the end of the day, both call for complete, life-long elimination of gluten. Having said that, there is no doubt in my mind that you have celiac disease and not NCGS.

Let me include this attachment to help you see the many ways gluten sneaks into our diet that need attention: https://duckduckgo.com/?q=The+gluten+free+diet+101&atb=v400-7__&ia=web

[ShelbyE720]

That’s a very enlightening perspective. I have done a lot of research on Celiac disease, but not a ton on NCGS yet. Discouragingly, on the internet you find everything from “this isn’t real” to “it’s very real, and needs to be taken very seriously”. 

It’s scary that a specialist would only give me a few sentences message on my test results to diagnose me. Sadly, that’s ALL I got (not even a phone call) and have to try to find answers myself. This place is truly awesome to offer support. Thank you for your insight! I feel a little less crazy that I am not over reacting.

I do have a follow up with dermatology this week to look into my skin issues. He was waiting on my GI doctors results before trying to diagnose me. I’ll be interested what his perspective is on everything. I’ve been suffering from persistent swollen/itching/burning lips as well as my vulva (my OB had no idea what the vulva was about-It is NOT a yeast infection.) Both have greatly reduced since going gluten-free! Also armpit burning/rashes, various random patches on my legs and (1 behind me knee even ulcerated for a couple weeks). 
 

This has been a wild journey and maybe my experience with this may help another person out there questioning if they are losing their mind.

[trents]

Essentially all the "veteran" celiacs on this forum will tell you that there is woeful knowledge about celiac disease within the medical community as a whole. My own diagnostic journey took the medical profession 13 years to arrive at the right conclusion. It started with the discovery of elevated liver enzymes that caused the rejection of a Red Cross blood donation when I was 37. General practitioners tested me for all the hepatitis varieties known to medicine and I didn't use alcohol so they could not explain it. In the meantime, my hemoglobin was steadily dropping as well as albumin and total protein. I was employed by a healthcare/hospital system and as part of my benefits I got a CBC and a CMP every year so I could track these things. The monkey wrench in the diagnostic gear process was that I had little or no GI distress so, back then, doctors did not consider that the problem might be celiac disease because it was mistakenly believed that if you had celiac disease you would necessarily have major GI distress. They didn't know back then that many celiacs are "silent". After running a number of tests not designed to detect celiac disease, my GP at the time (about the year 2000) said, "I don't know why your liver enzymes are elevated. May that's just the way you are." That was not an acceptable answer. The liver is a pretty important organ. So, I booked an appointment with a GI doc on my own. The first thing he did was run celiac antibody tests, which were positive. Then he did the biopsy to confirm. Within three months of beginning my gluten free journey my liver enzymes were within normal range again. We now know that about 20% of celiacs have elevated liver enzymes. 

Unfortunately, my story is all too common in the celiac community. It often takes 10 years or more to get diagnosed because most GP's and even a lot of GI's aren't up to speed on gluten-related disorders. Especially if they have been out of medical school for years, they may be operating on very dated information. And this is the value of an online community like this one. We are focused on gluten-disorders and it's not just one of a 1000 other gastroenterological problems that GP's and GI's have to deal with. We follow the research on gluten-related disorders regularly and aren't distracted by a host of other medical conditions that physicians have to deal with. Some of our moderators on this forum have medical expertise. I know one is a nurse and another is a biochemist. So we have some people who help us dive a little deeper sometimes.

And you might be interested to know that we have some contributors on this forum with celiac disease who have had negative antibody scores but positive biopsies and vice versa. Some who have DH have no enteric involvement. Actually, gluten disorders are proving to be much more complex than we once thought and sometimes defy the nice little boxes we like to put things in.

[Scott Adams]

44 minutes ago, ShelbyE720 said:

It’s scary that a specialist would only give me a few sentences message on my test results to diagnose me. Sadly, that’s ALL I got (not even a phone call) and have to try to find answers myself.

It's sad to hear that ~27 years after my diagnosis this approach is still common! This is exactly how my diagnosis arrived, just a one line note from my doctor who advised me to avoid gluten.

[Russ H]

5 hours ago, ShelbyE720 said:

Meanwhile I had asked for the genetic testing to be really sure and to my surprise, I was negative for the genes associated with Celiac. My doctor then said “there’s no way it is Celiac Disease, maybe you improved bc you are just Gluten sensitive and just stay gluten-free if it helps”

You certainly can have coeliac disease while not having the common HLA types although it is not common - about 1% of people with coeliac don't have the common HLA types.

https://www.coeliac.org.uk/information-and-support/coeliac-disease/about-coeliac-disease/causes/genetics/

Edited November 13, 2023 by Russ H

[ShelbyE720]

Thanks Russ! 
makes you wonder why my doctor dismissed it as an etiology so quickly? * sigh*… I just don’t understand.

[trents]

4 hours ago, ShelbyE720 said:

Thanks Russ! 
makes you wonder why my doctor dismissed it as an etiology so quickly? * sigh*… I just don’t understand.

I suspect your doctor was unaware of the factoid shared by Russ H. Also, modern medicine and the payer system are totally driven by statistics and efficiency. If it isn't likely it gets tossed out because they won't invest the time necessary to deal with things outside the box. It's economically inefficient to do so.

Edited November 14, 2023 by trents

[AnnaNZ]

Did your doctor share with you your actual genetic results?

[ShelbyE720]

Yes, I did get a copy of my exact genetic results. The variants are as follows: 

HLA DQ A1: 01 and 05

HLA DQ B1: 0301 and 0503

[AnnaNZ]

It looks like you and I have the same genetic variant but here in NZ they only seem to list the troublesome (?) markers.

Mine was given to me as:

DQA1*05 and DQB1*03:01 (DQA1*05) = DEMONSTRATED

Relative risk for coeliac disease:

HLA-DQA1*05 (Very Low)

Your doctor was incorrect saying there is no way you have coeliac disease. The chance may be very low but that is different from impossible.

I am in the early stages of getting a diagnosis and unfortunately gave up gluten before I had the antibody test. You have a lot worse symptoms than me though.

Are you from the US? Do you know where your genes came from generations ago?

I am 50% Norwegian, 25% German, 12% English and 12% Scottish.

[knitty kitty]

Those ARE genes for Celiac.  

Double check my sources....

Genetic susceptibilty and celiac disease: what role do HLA haplotypes play?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502200/

"HLA-DQ2 heterodimers are encoded by DQA1*05 and DQB1*02 alleles...."

"...DRB1*03:01 allele, which was first associated with celiac disease risk..."

And...

HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482388/

And...

Genetic susceptibilty and celiac disease: what role do HLA haplotypes play?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502200/

And...

HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, Are More Expressed Than Non-Predisposing Alleles and Are Coordinately Regulated

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678473/

[ShelbyE720]

AnnaNZ- I am roughly 50% Germanic Europe and 25% England & Northwestern Europe with a few other small amounts from 3 other regions… I hope you get some answers soon!

knitty Kitty- That is SO interesting! I never would have thought that with how the genetic information was presented to me. I feel like it may be safe to say that I actually DO have celiac disease. This diagnosis really does explain so much…

[knitty kitty]

Welcome to the Celiac Club, @ShelbyE720!  

Deficiencies in certain vitamins can cause skin changes.  I had a similar rash in the same places.  It went away when I supplemented Riboflavin B2.  Deficiencies in vitamins like B12, Vitamin C and Niacin can cause skin changes, too.

Here's an article with which to compare yours.

Cutaneous signs of nutritional disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721081/

Correcting nutritional deficiencies is part of proper follow up care for Celiacs. 

Keep us posted on your progress!

[trents]

@ShelbyE720, it seems your GI doc gave you a bum steer on the genetic report.

kk, thanks for those links. I didn't understand a lot of it but I think I gleaned that how the genetic report is presented can be confusing such as obscure the data most of us look for.

[ShelbyE720]

I wanted to update everyone on my diagnosis in case this may ever help someone else reading this thread.

Today I had an appointment with my dermatologist whom took the time to dive into all my test results and even consult with another GI doctor he knows. He came to the conclusion that he believes without a doubt that I DO actually have Celiac Disease, despite a negative test result from my genetic screening. He explained that we just simply do not know everything about the genes with Celiac and the diagnosis absolutely can’t be ruled out by that alone when I had 1) positive antibody test, 2) positive biopsy, 3) responded to the gluten free diet and 4) have the skin conditions associated with the disease.

Today I feel a great sense of relief to have a formal diagnosis and to stop questioning if gluten free is what I need to be doing for life. I feel validated and grateful for a doctor that finally took time and thought to treat me. Today is a good day and I never thought I would feel that way while being told I have a life long disease.

[Scott Adams]

I agree with your doctor, and every couple of years it seems that new genes responsible for celiac disease are being discovered.

[Raquel2021]

On 11/13/2023 at 11:46 AM, ShelbyE720 said:

I’m hoping someone here can give me some hope about my current situation!

I’ve spent the last 6 months seeing numerous doctors looking for answers to various wild problems I’m having. I went from perfectly healthy to quickly deteriorating over the course of the last few months. It started with extreme fatigue and cracking lips and turned into skin rashes (doesn’t look like DH though) chronically swollen lips, hair loss, anxiety, dizzy, extreme nausea, vomiting,chronic diarrhea. I lost 10lbs in 6 weeks. 
 

finally made it to GI specialist. Had a barely positive antibody test (15) for 1 antibody, but also had a positive biopsy (Villous atrophy with increased lymphocytes). I was told it was Celiac Disease and go gluten-free, so I did and my most extreme symptoms (vomiting/diarrhea) did stop. Meanwhile I had asked for the genetic testing to be really sure and to my surprise, I was negative for the genes associated with Celiac. My doctor then said “there’s no way it is Celiac Disease, maybe you improved bc you are just Gluten sensitive and just stay gluten-free if it helps”

So now I don’t know what to think! (I have also had a blood test to check for wheat allergy that was negative). Do I just stick to this diet hoping it’s an intolerance causing all these issues? Has anyone ever had Celiac without the common genes? Do I keep looking for other answers or accept it’s just NCGS? 

I never had genetic testing done. Just antibodies and positive endoscopy.  My GI Dr told me I had celiac for sure. Maybe there was an error with your genetic testing.  If the gluten-free diet has helped I would stick with it.

[Raquel2021]

On 11/13/2023 at 10:52 PM, knitty kitty said:

Welcome to the Celiac Club, @ShelbyE720!  

Deficiencies in certain vitamins can cause skin changes.  I had a similar rash in the same places.  It went away when I supplemented Riboflavin B2.  Deficiencies in vitamins like B12, Vitamin C and Niacin can cause skin changes, too.

Here's an article with which to compare yours.

Cutaneous signs of nutritional disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721081/

Correcting nutritional deficiencies is part of proper follow up care for Celiacs. 

Keep us posted on your progress!

@knitty kitty can you please list the brand of B vitamins you take? I am still looking for one that wont give me insomnia.  I have tried taking them first thing in the morning. 

[knitty kitty]

@Raquel2021,

More than happy to.  I like Life Extension brand.

B Complex...

https://www.lifeextension.com/vitamins-supplements/item01945/bioactive-complete-b-complex

Benfotiamine  100 mg

https://www.lifeextension.com/vitamins-supplements/item00920/benfotiamine-with-thiamine

Benfotiamine 250 mg (you may want to start with the 100 mg and increase dose when symptoms return or fail to resolve)

https://www.lifeextension.com/vitamins-supplements/item00925/mega-benfotiamine

Magnesium Threonate

https://www.lifeextension.com/wellness/supplements/magnesium-threonate-benefits?psafe_param=1&gad_source=1&gclid=EAIaIQobChMIyMSrj4rKggMV6jjUAR1oPwGREAAYASAAEgIjo_D_BwE

https://www.lifeextension.com/search#q=Mag threonate&t=coveo4A2453FD

[Raquel2021]

9 hours ago, knitty kitty said:

@Raquel2021,

More than happy to.  I like Life Extension brand.

B Complex...

https://www.lifeextension.com/vitamins-supplements/item01945/bioactive-complete-b-complex

Benfotiamine  100 mg

https://www.lifeextension.com/vitamins-supplements/item00920/benfotiamine-with-thiamine

Benfotiamine 250 mg (you may want to start with the 100 mg and increase dose when symptoms return or fail to resolve)

https://www.lifeextension.com/vitamins-supplements/item00925/mega-benfotiamine

Magnesium Threonate

https://www.lifeextension.com/wellness/supplements/magnesium-threonate-benefits?psafe_param=1&gad_source=1&gclid=EAIaIQobChMIyMSrj4rKggMV6jjUAR1oPwGREAAYASAAEgIjo_D_BwE

https://www.lifeextension.com/search#q=Mag threonate&t=coveo4A2453FD

Thank you and you have no issues with insomnia? 

[knitty kitty]

3 hours ago, Raquel2021 said:

Thank you and you have no issues with insomnia? 

Yes, I do have trouble with insomnia sometimes.  When I do, I take the amino acid L-Tryptophan, a form of Niacin B 3, that helps make serotonin and melatonin.  I take a magnesium glycinate or magnesium threonate, and a Pyridoxine B 6 supplement (low dose).  Pyridoxine helps with dreaming, an important part of restorative sleep.  

https://pubmed.ncbi.nlm.nih.gov/29665762/

[Raquel2021]

Thanks. For me any time I take B complex I find I have a terrible sleep. It gives me too much energy.